a Department of Chemistry , University of Zabol , Zabol , Iran.
b Department of Chemistry , University of Sistan and Baluchestan , Zahedan , Iran.
J Biomol Struct Dyn. 2018 Aug;36(11):2807-2821. doi: 10.1080/07391102.2017.1367723. Epub 2017 Sep 1.
Ligand binding studies on carrier proteins are crucial in determining the pharmacological properties of drug candidates. Here, a new palladium(II) complex was synthesized and characterized. The in vitro binding studies of this complex with two carrier proteins, human serum albumin (HSA), and β-lactoglobulin (βLG) were investigated by employing biophysical techniques as well as computational modeling. The experimental results showed that the Pd(II) complex interacted with two carrier proteins with moderate binding affinity (K ≈ .5 × 10 M for HSA and .2 × 10 M for βLG). Binding of Pd(II) complex to HSA and βLG caused strong fluorescence quenching of both proteins through static quenching mechanism. In two studied systems hydrogen bonds and van der Waals forces were the major stabilizing forces in the drug-protein complex formation. UV-Visible and FT-IR measurements indicated that the binding of above complex to HSA and βLG may induce conformational and micro-environmental changes of two proteins. Protein-ligand docking analysis confirmed that the Pd(II) complex binds to residues located in the subdomain IIA of HSA and site A of βLG. All these experimental and computational results suggest that βLG and HSA might act as carrier protein for Pd(II) complex to deliver it to the target molecules.
配体与载体蛋白的结合研究对于确定候选药物的药理学性质至关重要。在这里，合成并表征了一种新的钯（II）配合物。通过使用生物物理技术和计算建模研究了该配合物与两种载体蛋白（人血清白蛋白（HSA）和β-乳球蛋白（βLG））的体外结合研究。实验结果表明，钯（II）配合物与两种载体蛋白的相互作用具有中等结合亲和力（对于 HSA，K≈5×10^-5 M；对于βLG，K≈2×10^-5 M）。钯（II）配合物与 HSA 和βLG 的结合通过静态猝灭机制导致两种蛋白质的强荧光猝灭。在两个研究系统中，氢键和范德华力是药物-蛋白质复合物形成的主要稳定力。紫外-可见和傅里叶变换红外测量表明，上述配合物与 HSA 和βLG 的结合可能诱导两种蛋白质的构象和微环境变化。蛋白质-配体对接分析证实，钯（II）配合物与 HSA 的亚域 IIA 中的残基和βLG 的 A 位结合。所有这些实验和计算结果表明，βLG 和 HSA 可能作为载体蛋白将钯（II）配合物递送至靶分子。
